A Study In Patients With Neuropathic Pain From Diabetic Peripheral Neuropathy (DPN)

Study PXN110448: A Dose-response Study of XP13512, Compared With Concurrent Placebo Control and LYRICA(Pregabalin), in Subjects With Neuropathic Pain Associated Withdiabetic Peripheral Neuropathy (DPN)

The purpose of this study is to determine whether gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn is effective in the treatment of neuropathic pain associated with diabetic peripheral neuropathy(DPN)

This is a dose-response study of XP13512 compared with concurrent placebo control and LYRICA (pregabalin), in subjects with neuropathic pain associated with DPN. Three doses of XP13512 (1200 mg/day, 2400 mg/day and 3600 mg/day) are being evaluated for the management of neuropathic pain associated with DPN. Approximately 392 subjects from 70 to 80 participating sites in the US will be randomized to receive either XP13512 at the above mentioned doses, placebo or pregabalin (300mg/day).

Inclusion criteria:

• 18 years or older
• Female subjects are eligible to enter if of non-childbearing potential or not lactating, has a negative pregnancy test and agrees to use a specified highly effective method for avoiding pregnancy
• Documented medical diagnosis of Type 1 or 2 diabetes including:
• Stable glycemic control for 3 months defined as <25% change of routine insulin, <50% change of routine oral anti-diabetic agent dose and HbA1c < 8%. (HbA1c of 8 to 11% eligible if attempts to improve diabetic control failed)
• DPN defined by:
• Bilateral reduced or absent reflexes at the ankles, or
• Bilateral impaired vibration, pinprick, fine touch or temperature perception in the distal lower extremities And
• Persistent distal burning or dull pain in the feet, or
• Persistent proximal aching pain in the legs, or
• Paroxysmal electric, shooting, stabbing pain, or
• Dysasthesias, or
• Evoked pain And
• history of pain for at least six months and no greater than five years attributed to DPN (refers to duration of pain)
• Baseline 24-hour average daily pain intensity score >4.0 as measured on an 11 point pain intensity numerical rating scale
• Provides written informed consent in accordance with all applicable regulatory requirements

Exclusion criteria:

• Other chronic pain conditions not associated with DPN. However, the subject will not be excluded if:
• The pain condition is located at a different region of the body, and
• The pain intensity of this condition is not greater than the pain intensity of the DPN, and
• The subject can assess their DPN independently of other pain condition.
• Other causes of neuropathy or lower extremity pain
• Is unable to discontinue prohibited medications or non-drug therapies or procedures throughout the duration of the study
• Hepatic impairment defined as ALT or AST > 2x upper limit of normal (ULN) or alkaline phosphatase or bilirubin > 1.5x ULN
• Chronic hepatitis B or C
• Impaired renal function defined as either creatinine clearance < 60 mL/min or requiring hemodialysis
• Corrected QT (QTc) interval >450 msec or QTc interval >480 msec for patients with Bundle Branch Block
• Uncontrolled hypertension at screen (sitting systolic >160 mmHg and/or sitting diastolic >90 mmHg
• Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drug(s)
• Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GEn or pregabalin, or, in the investigator's judgment:
• Is considered to be clinically significant and could pose a safety concern or,
• Could interfere with the accurate assessment of safety or efficacy, or,
• Could potentially affect a subject's safety or study outcome
• Meets criteria defined by the DSM-IV-TR for a major depressive episode or for active significant psychiatric disorders within last year
• Depression in remission, with or without antidepressant treatment, may participate, unless stable antidepressant regimen is a prohibited medication
• Antidepressant medication may not be changed or discontinued to met entry criteria and must be stable for at least 3 months prior to enrollment
• History of clinically significant drug or alcohol abuse (DSM-IV-TR). Benzodiazepines or atypical benzodiazepines as hypnotic sleep agents permitted
• Currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device
• Has participated in a clinical study and was exposed to investigational or non-investigational drug or device:
• Within preceding month for studies unrelated to DPN, or
• Within six months for studies related to DPN
• Treated previously with GEn
• History of allergic or medically significant adverse reaction to investigational products (including gabapentin or pregabalin) or their excipients, acetaminophen or related compounds